espite
years of searching, researchers have yet to discover a human gene that
controls blood pressure or contributes to hypertension. The worldwide
effort has generated a list of chromosome regions that may contain these
genes but no specific genes or variants.

Now, a region of chromosome 6 has been added to the list. British researchers
discovered the region by “scanning” the genomes of 2,000 pairs
of siblings from families with severe hypertension for DNA they had in
common. In addition to chromosome 6, several other areas were implicated,
but the statistical evidence was modest.

The next step is to screen the regions for gene candidates, but the researchers
acknowledge that whatever they find will not be the whole story on the
genetics of hypertension.

Where are all the blood-pressure genes?

Indeed, the story seems to be that many genes (or variants) contribute
in small degrees to inherited differences in blood pressure, and that
different genes may confer risk for hypertension in different populations.

“We really don’t know how many blood pressure genes there
are,” says Mark J. Caulfield of Queen Mary’s School of Medicine,
London, who led the new study. “We hope they number 5 or 10, but
there could be 20 or more.”

As with other complex diseases, like schizophrenia and heart disease,
pinpointing genetic risk factors for hypertension will not be easy.

Consider a recent analysis of data from genome scans for hypertension
genes published in the scientific literature. This “meta-analysis”
found that no single chromosome region consistently had large effects
on blood pressure or hypertension in all the study populations. It was
published in the American Journal of Hypertension in February.

The original genome scans were done at medical centers in the United
States as part of the National Heart, Lung, and Blood Institute Family
Blood Pressure Program (FBPP). The subjects came from different ethnic
groups and represented the racial diversity of the U.S. population.

The new research is part of the Medical Research Council’s BRItish
Genetics of HyperTension (BRIGHT) study. The findings appear in The
Lancet along with a commentary entitled “Where are all the blood-pressure
genes?”

Citing the challenges of finding genes underlying common diseases, the
commentary’s author, Stephen B. Harrap of the University of Melbourne,
Australia, suggests that it simply may not be possible to discover gene
variants for hypertension that would be valuable in the diagnosis of the
disease.

Rather than search for every gene variant underlying hypertension, he
argues, the field needs to “search for molecular clues to the common
physiological mechanisms underlying disease.”

The study in The Lancet may ultimately lead to new risk factors
for severe hypertension. None of the chromosome regions in the study was
associated with the disease in humans until now. But part of chromosome
2 corresponds to a region of the rat genome associated with elevated blood
pressure.

“We are encouraged by this because it means we may have found a
region that actually contains genes” for hypertension, says Caulfield.
“We’re making some progress, though perhaps not as much as
we would like.”

“If finding the genes were easy, we would not have undertaken such
large studies.”